This document arises from the HAI Europes Operating Grant 2011, which has received funding from the

European Union, in the framework of the Health programme. The views expressed in this publication are those of

the author, who is solely responsible for its content. The Executive Agency for Health & Consumers is not

responsible for any use of the information herein.

CHRONOLOGY: NIMESULIDE IN EUROPE

1985 -Nimesulide is first marketed in Europe.

1985 - Reports of serious adverse reactions to nimesulide begin to surface from across Europe.i ii

2002 - Finland and Spain withdraw the medicine from the market following cases of liver injury caused by

nimesulide. iii

Shortly afterwards, Finland alerted the EMA, which mandated representatives from Italy, the country

with the highest consumption of nimesulide, and Finland to report on the safety profile of the medicine.iv

2003 - Patients taking nimesulide have double the chance of suffering severe liver damage compared to the risk

posed by other non-steroidal anti-inflammatory, according to a recently published Italian study conducted on 397

500 patients between 1997 and 2001.v

2004 - Nimesulide -evaluation of the medicine.

Certain limitations are also imposed, such as a lower maximum dose.vi

2007 - Ireland suspends the sale of nimesulide after six cases of liver failure requiring liver transplants are

reported in association with the medicine.vii

2007 - This prompted the EMA to re-evaluate the safety profile of nimesulide, this time appointing Ireland as the

rapporteur. The EMA ruled that the data did not support a move to suspend the marketing of nimesulide across

Europe. However, the use of nimesulide is further restricted to a second-line treatment at the lowest effective

dose.viii

2008 - Over 570 cases of hepatic disorders associated with nimesulide are reported from across Europe since

1985.ix

2010 - Patients have 2.5 times higher risk of hospitalisation for acute liver damage with nimesulide than with

other non-steroidal anti-inflammatories,x according to a case-control study conducted between 2001 and 2004

but not published until this year.xi

2011 - The EMA affirms that the benefits of nimesulide-containing medicines continue to outweigh the risks,

while its use is restricted to treat only acute pain and menstrual pain.xii xiii

ii La revue prescrire. Nimesulide: patients still exposed to a risk of severe hepatitis (2011) URL:

http://english.prescrire.org/en/D888466637A59AC42A489AA0BEBB2235/Download.aspx iii EMA post-authorisation evaluation of nimisulide (2004) URL:

http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Nimesulide_31/WC500013818.pdf iv See EMA post-authorisation evaluation of nimisulide (2004)

v -steroidal anti-

vi See EMA post-authorisation evaluation of nimisulide (2004)

vii EMA Press Release - European Medicines Agency recommends restricted use of nimesulide-containing medicinal products (2009) URL:

http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500011199.pdf viii

See EMA Press Release (2009) ix See La revue prescrire (2011)

x Except with celecoxib, rofecoxib, diclofenac and ibuprofen

xi Pharmacoepidemiol Drug

Saf 2010; xii

The review of nimesulide was conducted in the context of a formal review under Article 31 of Directive 2001/83/EC, initiated in January 2010 at the request of the European Commission xiii

EMA Press Release - European Medicines Agency concludes review of systemic

nimesulide-containing medicines (2011) URL: www.ema.europa.eu/docs/en_GB/document_library/Press_release/2011/06/WC500107903.pdf

http://english.prescrire.org/en/D888466637A59AC42A489AA0BEBB2235/Download.aspxhttp://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Nimesulide_31/WC500013818.pdfhttp://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500011199.pdfhttp://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2011/06/WC500107903.pdf